Cornea

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Cornea:
doi: 10.1097/01.ico.0000263124.91639.4e
Symposium 2

Effect of Herpes Simplex Virus‐1 gD or gD‐IL‐2 DNA Vaccine on Herpetic Keratitis

Inoue, Tomoyuki M.D.; Inoue, Yoshitsugu M.D.; Hayashi, Kozaburo M.D.; Shimomura, Yoshikazu M.D.; Fujisawa, Yukio Ph.D.; Aono, Aki Ph.D.; Tano, Yasuo M.D.

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Abstract

Purpose: To evaluate the efficacy of DNA immunization using herpes simplex virus (HSV)-1 gD or gD-IL-2 (chimeric gene of gD and human IL-2) with reference to their immune responses and preventive effect on the development of murine herpetic stromal keratitis, based on our previous work.

Methods: Plasmids containing gD (pHSDneo1) or gD-IL-2 (pHDLneo1) were constructed, and gD or gD-IL-2 peptides were purified. BALB/c mice were immunized by hypodermal injection, subconjunctival injection, or topical eye drop twice at 7-day intervals. Attained anti-HSV immune reaction was estimated, including neutralizing antibody, delayed-type hypersensitivity (DTH) measured by the swelling of the ear pinna, and cytotoxic T lymphocyte (CTL) measured by 51Cr release from MHC-matched target cells by splenic and/or local lymph node cells. The corneas of a group of the immunized mice were challenged with CHR3 strain of HSV-1 (10 μL of 3 × 106 PFU/mL) 3 weeks after the last immunization. Clinical signs (stromal and epithelial keratitis) were scored.

Results: All gD- or gD-IL-2-immunized mice developed specific neutralizing antibody. Delayed-type hypersensitivity and CTL were obtained in gD DNA- or gD-IL-2 DNA-immunized mice. Chimeric DNA vaccine gD-IL-2 elicited higher DTH and more vigorous CTL activity. The scores of stromal keratitis for all gD- or gD-IL-2-immunized mice were significantly suppressed, although those of epithelial keratitis were not.

Conclusion: Immunization with gD or gD-IL-2 was effective against herpetic stromal keratitis. By focusing specifically on high induction of cell-mediated immunity, gD-IL-2 DNA could have possible clinical applications against HSV-1 in the future.

© 2002 Lippincott Williams & Wilkins, Inc.

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